Can biotech finally fix infertility?

Infertility care is now heavily structured around assisted reproduction technology (ART). IVF and its close relatives have become the default pathway, largely because they give clinicians control over the part of reproduction that can be influenced reliably, such as fertilisation and early embryo development.

But even in this highly optimised setting, outcomes still vary widely from one couple to the next. According to the European Society of Human Reproduction and Embryology (ESHRE), in 2020, the mean pregnancy rate per embryo transfer was about 33% after IVF and intracytoplasmic sperm injection (ICSI), about 36% after frozen embryo transfer, and around 51% after egg donation, with a success rate higher in younger patients.

IVF works often enough to have become the backbone of treatment, but it still leaves a lot of biology unaddressed. Implantation is a clear example. Successful implantation depends on a dialogue between embryo and endometrium, and when that dialogue fails, the embryo simply doesn’t take, in many cases without a clear explanation.

Reviews of recurrent implantation failure describe it as a persistent clinical phenomenon, affecting an estimated 10% of couples undergoing IVF and embryo transfer. If you can improve endometrial receptivity, reduce inflammation, or shift the local environment in a measurable way, you could theoretically raise the odds of success without changing the IVF process itself. Another blind spot is that assisted reproduction often works around underlying biology rather than correcting it, especially in cases of male factor infertility. Technologies such as ICSI can bypass many sperm-related barriers by design, but it’s not a direct treatment of the male reproductive problem itself.

Over time, ICSI also expanded well beyond clear male-factor indications in many settings, and there has been criticism that it is used where it doesn’t improve outcomes and may add cost and complexity. A 2025 analysis in Reproductive BioMedicine Online argues that ICSI should be limited to couples with male infertility, describing widespread overuse in ART4.

This is also where the female-centred dynamic of infertility care becomes hard to ignore. Even when infertility originates in the male partner, the most established solutions tend to move the clinical burden toward the female body: ovarian stimulation, egg retrieval, embryo transfer, and hormonal support. That’s not because clinics ignore male factors, but because the dominant toolbox is procedural and couples-focused, and the interventions that reliably change outcomes have historically been built around the female cycle and the IVF workflow.

“Although infertility is 50% men related, there is no ­approved treatment ­addressing this segment. There is no ­standard of care for half the population.” Florent Ferré, CEO of Igyxos

“The issue that we are facing with IVF is that more and more women don’t respond well to the hormonal stimulation, which is the first part of the IVF treatment, and therefore are not very successful when they go through the procedure. This is why there is a need for more effective treatment,” said Florent Ferré, CEO of Igyxos, a fertility-focused biotech based in France. Much of the current innovation isn’t trying to replace IVF or promise cures. It’s trying to intervene in the unresolved steps where IVF has blind spots.

Treating biology upstream

One reason fertility care has become so tightly organised around IVF is that it offers predictable control that drug-based approaches have struggled to deliver consistently. Hormone biology, in that setting, has often been used less as a way to correct underlying dysfunction and more as a means of making IVF cycles work through ovarian stimulation protocols, trigger injections, and luteal phase support. Endocrine signalling, in other words, has largely been folded into the IVF workflow rather than treated as a therapeutic target itself.

On the female side, hormone manipulation is central to controlled ovarian stimulation, but primarily to optimise egg yield and timing rather than restore ovarian function. On the male side, medical options are even more limited. “Although infertility is 50% men related, there is no approved treatment addressing this segment. In a couple, even if infertility is men-related, the healthy wife will go through the IVF, meaning there is no standard of care for half the population,” said Ferré.

Outside a narrow set of endocrine deficiencies or surgically correctable conditions, most male-factor infertility is managed procedurally: if sperm parameters are poor, IVF with ICSI can bypass the problem, but it does so without addressing the biological cause.

Targeting male infertility biology may become increasingly important over time, too. “Over the last 25 years, we have seen more and more sperm decline. We are looking at a decline of 2% to 2.5% every year. If this trend stays on track, by 2040, almost half of the men will be in a situation of low concentration,” noted Ferré.

According to Igyxos’ CEO, the first reason why the male factor of infertility has been overlooked comes from a cultural bias. “Also, infertility related to men was not well understood. And looking at the available data, it’s probably only since the 2000s that more studies confirmed that it’s not a woman’s issue, but a couple’s issue.”

That upstream gap, where reproductive biology sets the odds before IVF begins, is where Igyxos positions its approach. The French company is developing IGX12, a monoclonal antibody designed to potentiate the follicle-stimulating hormone (FSH), a regulator of gamete production in both sexes. The idea is not to administer FSH itself as a hormone therapy, which is already widely used in fertility care, but to modulate its activity.

Exogenous FSH is indispensable in ovarian stimulation, but its broader use as a therapeutic intervention has been harder to establish. In male infertility in particular, administering FSH has produced mixed results. Some patients show improvements in sperm parameters, while others do not, and clinicians have had a hard time predicting who will benefit.

Igyxos thinks that better pharmacology could change that equation. Improving FSH signalling can lead to better parameters upstream and more consistent ovarian responses in women undergoing ART, as well as improved spermatogenesis in men with compromised sperm production.

Downstream, this would mean fewer failed cycles, less extreme stimulation, and, in some cases, a reduced need to default immediately to the most invasive procedural options.

“Experiences such as ObsEva’s have shown how difficult it is to demonstrate a clinical benefit on ultimate endpoints like ongoing pregnancy or live birth, endpoints that are long, variable, and unforgiving.” Agnès Arbat, CEO of Oxolife

“In animal models, IGX12 has been able to restore spermatogenesis in cases of azoospermia, the worst possible scenario. If we are able to translate these data in human, then IGX12 could become a first-line option for men facing low concentration,” explained Ferré.

In women, the strategy for the phase 2 trial of IGX12 is to address those who respond poorly to the first step of IVF, gonadotropin stimulation.
Comparable efforts remain rare, but they do exist. In the U.S., ReproNovo is also pursuing oral therapies targeting hormonal dysfunction and impaired spermatogenesis rather than procedural workarounds. Another U.S. company, Celmatix, is working on upstream hormone-pathway programs, including one involving FSH, but frames the problem primarily through ovarian health.

Other companies, such as New York-based Gameto, are also working on fertility with a more upstream, biology-driven approach. Its ovary-in-a-dish platform is designed to model meiosis and early oocyte development in vitro, stages of egg formation that are currently not directly manipulable within IVF workflows.

Improving IVF odds without replacing it

Fertilisation and early embryo development can be managed and optimised in the lab, but whether an embryo actually establishes a pregnancy still depends on biological parameters: endometrial receptivity, immune signalling, uterine contractility, and early placentation. If you can make the uterus more receptive at the moment of implantation, you might raise success rates without changing the IVF process itself.

Oxolife is currently working on that segment. The Barcelona-based company is developing OXO-001, a non-hormonal oral drug that acts on the endometrium to enhance implantation during IVF and ICSI cycles. “Unlike current IVF workflows, which focus primarily on selecting the best embryos, OXO-001 acts directly on the endometrium. It modulates the expression of proteins involved in adhesion, invasion, and the completion of embryo implantation, improving the uterine environment rather than compensating for its limitations,” explained the company’s CEO, Agnès Arbat.

OXO-001 is an adjunct therapy aimed at increasing the probability that an embryo transfer results in a pregnancy and, ultimately, a live birth. In phase 2, Oxolife reported an ongoing pregnancy rate at 10 weeks of 46.3% versus 35.7% in the placebo group, and a live birth rate of 42.6% versus 35.7%.

But with implantation adjuncts, early signals don’t always survive scale-up. “Implantation is an exceptionally complex biological process, and experiences such as ObsEva’s have shown how difficult it is to demonstrate a clinical benefit on ultimate endpoints like ongoing pregnancy or live birth, endpoints that are long, variable, and unforgiving.”

ObsEva was once seen as one of Europe’s most promising fertility-focused biotechs, with a strategy around drugs designed to improve pregnancy outcomes by acting on uterine biology rather than the IVF procedure itself.

Its most advanced program, nolasiban, targeted oxytocin receptors and was developed as an oral treatment intended to improve implantation and pregnancy rates during embryo transfer. Uterine contractions around the time of transfer were thought to interfere with implantation, and dampening that activity could, in theory, create a more receptive environment for the embryo.

Early studies suggested potential benefits, and the program progressed into late-stage development. But in phase 3 trials, nolasiban failed to demonstrate a meaningful improvement in live birth rates. Without a clear efficacy signal on the endpoints that matter most to patients and regulators, ObsEva’s program collapsed. The company ultimately filed for bankruptcy in early 2024.

The lesson is not that implantation biology is irrelevant, but that endpoints can be unforgiving. Programs that position themselves as IVF adjuncts must show not just biological activity, but a clear and clinically meaningful improvement over procedures that are already effective.

Treating the fertility environment

For a large subset of patients, infertility is a chronic state, and endometriosis is the clearest example of that category. Endometriosis affects roughly one in ten women of reproductive age, and it is strongly associated with infertility. The clinical effect is that many patients are funnelled into ART, not because IVF is the ideal treatment, but because it is the most reliable workaround once the underlying condition has already altered reproductive potential.

Indeed, a recent study led on more than four million women over 30 in the U.K. suggests that women suffering from infertility issues are twice as likely to be diagnosed with endometriosis. However, the same study suggests that endometriosis patients had 4 times more chances of pregnancy compared to women with infertility due to other factors. The study also specified that this was particularly true when the disease was diagnosed early.

While endometriosis is common, it is often diagnosed late, and delays can stretch for years, up to a decade, before patients receive a diagnosis. A delayed diagnosis logically compresses the reproductive timeline.

This diagnostic delay is where new approaches to fertility are beginning to emerge. One example is Viramal, a company focused on women’s health conditions that sit upstream of fertility outcomes, including endometriosis. Rather than positioning itself as an IVF outcomes company, Viramal targets the tissue environment that makes conception harder in the first place, particularly when the disease is diagnosed late.

Viramal’s lead program, VML-0501, is being tested in phase 2b as a locally delivered treatment for endometriosis. The treatment acts directly on the pelvic tissue, and while pregnancy isn’t the primary endpoint, the company argues that addressing the inflammatory environment has consequences on fertility.

Viramal is not alone in approaching infertility through the lens of reproductive tissue health. A small group of biotechs is exploring how chronic inflammatory and structural conditions of the reproductive tract shape fertility. In Europe, Gesynta Pharma is pursuing a non-hormonal strategy in endometriosis with vipoglanstat, an mPGES-1 inhibitor designed to dampen inflammatory pathways without suppressing ovarian function. Like Viramal, the premise is that improving the underlying tissue environment may preserve or restore fertility indirectly, even if pregnancy itself is not the primary trial endpoint. In late 2025, Gesynta started phase 2 for vipoglanstat in the U.K.

In the U.S., companies such as Forendo Pharma, acquired by Organon in 2021, have pursued non-hormonal strategies aimed at modulating endometrial and pelvic tissue biology, looking into alternatives to systemic hormone suppression to preserve reproductive potential. However, in 2025, the company announced its endometriosis candidate, OG-6219, did not meet its endpoint in phase 2.

Another emerging, still highly exploratory, biological angle in fertility research is the role of the reproductive tract microbiome in implantation and early pregnancy. Certain microbiome profiles could be associated with both favourable and unfavourable prognosis in IVF settings, though the field is far from validated clinical tools and remains an active area of basic research rather than a therapeutic category.

A small number of groups in Europe are looking into whether modulating the reproductive microbiome could influence fertility. The Netherlands-based ARTPred initiative has run clinical investigations looking at how urogenital microbiome composition might predict implantation outcomes before IVF, and is also exploring targeted probiotic formulations for cases with unfavourable profiles. Similarly, Denmark’s Freya Biosciences is developing microbial immunotherapy approaches focused on modulating inflammation associated with vaginal dysbiosis, an imbalance in the vaginal microbiota that can disrupt local immune signalling that has been linked to reproductive outcomes.

The elephant in the room: funding

IVF has made the infertility burden more manageable, but it has also shaped the field around what clinics can control procedurally while leaving the hardest biology to variability and repeated cycles.

The investment story sits awkwardly on top of that, largely because fertility occupies an uncomfortable category in healthcare financing. Clinically, infertility is a couple’s condition, with male biology contributing materially to outcomes. Financially, however, it is still often bundled into women’s health, with all the market-sizing shortcuts that label can trigger.

Women’s health is frequently described as underfunded; only 1% of healthcare research and innovation goes to female-specific conditions beyond oncology. “Women’s health” is often treated as a narrow vertical, frequently reduced to reproductive care. Yet women’s health outcomes extend far beyond reproduction and reproduction itself is not a women-only issue.

The companies emerging now are not replacing IVF so much as trying to make parts of reproduction less of a black box. This new wave of companies will live or die on unforgiving endpoints, but also on whether the field can be framed as a mainstream medical need rather than a niche category. As Florent Ferré put it, borrowing a characteristically French expression, “Il faut remettre l’église au milieu du village,” literally, to put the church back at the center of the village. In other words, there are still quite a lot of misconceptions around fertility, and the record needs to be set straight in order for the field to accelerate.

This article was originally published in European Biotechnology Magazine Spring 2026.